This application represents a proposal for the training of doctoral candidates in the pharmacological sciences. It is conceived as a broadly based training program which relies not only on the existing strong program in Pharmacology and Toxicology, but also upon the pharmacologically or toxicologically related interests of gifted researchers and teachers in other disciplines. These include individuals from the departments of Physiology, Biochemistry, Anatomy, Urology, Anesthesiology and the Appalachian Laboratory for Occupational Safety and Health. These are individuals who have clearly demonstrated their interests in pharmacological research both through their independent research and their collaborative research efforts with members of the Department of Pharmacology and Toxicology. Some of the specific research areas are central nervous system pharmacology, cardiovascular pharmacology, renal physiology/pharmacology, endocrine pharmacology, environmental pharmacology, autonomic pharmacology, pulmonary pharmacology and renal, hepatic and pulmonary toxicology. All research is aimed at hypothesis driven investigation of mechanisms with an emphasis on biochemical, cellular, electrophysiological and molecular techniques. The areas will be available to the trainees including basic and disease- related aspects. Training will be accomplished through formal course work, seminars, visiting lecturer program, laboratory rotation program, advanced specialty laboratory technique training and through close faculty-student, advisor-advisee interactions. Most trainees will enter the program with a BA or BS degree in chemistry or biology,~although it is anticipated that several will possess a degree in pharmacy or medicine. It is requested that we accept 6 trainees per year. It is anticipated that approximately 4 1/2-5 years will be required for the trainee to be awarded the Ph.D. degree. The primary training facilities will be in the Department of Pharmacology and Toxicology although laboratories in other departments will also be utilized. The Department of Pharmacology and Toxicology at West Virginia University has approximately 14,000 sq. Ft., most of which is designated as research space. Areas for the specific use of radioactive materials, cell culture work and specialized central facilities are present. The facilities are well equipped to pursue both classical pharmacological studies and biochemical or molecular problems.